Approaches to Initial Therapy for Patients With Aggressive DLBCL

Julie Vose, MD, University of Nebraska Medical Center, Omaha, Nebraska provides insight into classification and novel approaches for initial therapies for patients with aggressive diffuse large B-cell lymphoma (DLBCL) at the 2022 Lymphoma, Leukemia & Myeloma Congress in New York.

Transcript:

Hi, I'm Dr. Julie Vose from University of Nebraska Medical Center, where I'm Chief of Rheumatology, Oncology, and their lymphoma expert. I am at the 2022 Leukemia, Lymphoma, Myeloma Congress in New York in October, and just wanted to give you an overview of the talk that I gave.

I gave a talk on diffuse large B-cell lymphoma and some of the updates with respect to the World Health Organization (WHO) classification 5th edition that just came out. There are 17 different subtypes of diffuse large B-cell lymphoma, many of which are the same as the old classification, but some of which are new or combined categories, and it's important to look at the differences between the 4th edition and 5th edition so that when you get your pathology report you know exactly what you're dealing with. Some of the old ones were combined into new categories, incorporating things like [central nervous system] CNS lymphoma and testicular lymphoma, and then combinations of the old ones using our genetic classifications.

It's very important, because a lot of these subtypes that we're now understanding the genetic classifications of really help us to try to formulate different treatment options for higher risk patients that we may want to consider treatment options on relapse or in the future. There are differences in the genetic subtypes we used to call ABC versus GCB. Now, we know, there's many different sub-classifications within those subtypes. We're understanding more and more that some of these may need different treatments. I talked about those as well, and the heterogeneity and the different subtypes of diffuse large B-cell.

We used to think that all diffuse large B-cell was the same; we now know that's certainly not true. A lot of the different genetic subtypes behave differently and likely will need different treatment options yet to be understood. During the conference I talked about some different classical subtypes, such as primary mediastinal B-cell lymphoma. I talked about some of the information on the genetics of that and how it possibly could be treated differently. Information shows that most patients with this type of lymphoma that receive dose adjusted R-EPOCH chemotherapy do quite well even without mediastinal radiation as compared to historical information where R-CHOP plus mediastinal radiation was used and had higher relapse rate, yet higher toxicity. I definitely would choose to dose just R-EPOCH in this subtype of patients.

In addition, I also talked about double-expressor or double-hit lymphomas and some of the differences between these as far as outcomes and potential for differences in treatments. The double-expressor lymphomas may have a little bit worse outcome, but don't necessarily change our treatment strategies for those patients, whereas double-hit lymphomas with genetic subtypes, and high-grade lymphomas, we may treat differently with respect to more aggressive regimens than typical R-CHOP, for example. Some of the dose suggested R-EPOCH or higher intensity regimens, such as hyper-CVAD with rituximab may have better outcomes for this double-hit lymphomas.

I also talked about some of the double-hit lymphomas, with respect to the differences and some of the pathology that we need to look at. There are some new areas, such as the high-grade lymphomas that are not the double-hit lymphomas that may also have a worse outcome. It's unclear necessarily what treatment to give those patients. And then there's some of the subtypes that appear to be like Burkitt lymphoma, which we may want to treat with the very intensive regimens, such as the CODOX-M/IVAC or the Magrath regimen, or other very aggressive regimens. A standard diffuse large B-cell lymphoma that's not a double-hit, we can typically treat with standard of care R-CHOP. However, we certainly can still continue to use the International Prognostic Index to help us prognosticate these patients.

I talked about some of the new things with respect to clinical trials with adding the polatuzumab vedotin to the R-CHOP regimen. That's been looked at in a prospective randomized trial and does show an improvement in progression-free survival for the patients with diffuse large B-cell lymphoma. Although at the time of reporting there was no increase in overall survival, possibly due to inadequate follow-up or the ability to salvage these patients with regimens such as kinase therapy and transplant or CAR T-cell after relapse. We have to have further follow-up to find that. This regimen is currently not FDA-approved in the US, but polatuzumab is clinically available and could potentially be used, although insurance coverage may be still an issue.

Going forward, we're going to continue to understand the various aspects of diffuse large B-cell lymphoma, how to treat these patients, how to put them into different categories and maybe use different treatments. And for patients with localized disease, we've continued to try to decrease the amount of treatment that we're doing. For example, the FLYER study, decreasing the treatment from 6 cycles to 4 cycles, did appear to have a standard outcome that was just as good with 4 cycles of R-CHOP plus 2 additional rituximab cycles, as compared to 6 R-CHOPs alone. This may be continued, trying to decrease the amount of treatment for very limited stage diffuse large B-cell lymphoma.

I think we're going to be able to understand this and to use this, for example, trying to treat our patients with a lot of comorbidities, or elderly patients, perhaps with agents that are substituted, such as etoposide for the anthracycline. Or, to use reduced doses of treatment such as mini-CHOP, maybe something in the elderly or infirm population to use as well. Thankfully, we’re understanding lymphoma and diffuse large B-cell lymphoma much more, and hopefully, through clinical trials, we’ll be able to improve our knowledge in the future.

Source:

Vose J. Approaches to Initial Therapy for Patients With Aggressive Lymphoma. Presented at Lymphoma, Leukemia & Myeloma Congress; October 18-22, 2022; New York, NY.